Illness caused by pathogenic strains of Vibrio bacteria incurs significant economic and health care costs in many areas around the world. In the Chesapeake Bay, the two most problematic species are V. vulnificus and V. parahaemolyticus, which cause infection both from exposure to contaminated water and consumption of contaminated seafood. We used existing Vibrio habitat models, four global climate models, and a recently developed statistical downscaling framework to project the spatiotemporal probability of occurrence of V. vulnificus and V. cholerae in the estuarine environment, and the mean concentration of V. parahaemolyticus in oysters in the Chesapeake Bay by the end of the 21st century. Results showed substantial future increases in season length and spatial habitat for V. vulnificus and V. parahaemolyticus, while projected increase in V. cholerae habitat was less marked and more spatially heterogeneous. Our findings underscore the need for spatially variable inputs into models of climate impacts on Vibrios in estuarine environments. Overall, economic costs associated with Vibrios in the Chesapeake Bay, such as incidence of illness and management measures on the shellfish industry, may increase under climate change, with implications for recreational and commercial uses of the ecosystem.